The research program will focus on the human platelet alpha-adrenergic receptor. The receptor will be characterized using ligand binding assays. The primary ligand to be used is the partial agonist (H3)-p-aminoclonidine. The effects of monovalent cations and guanine nucleotides on ligand binding will be determined. The receptor will be solubilized using the detergent digitonin and will be assayed using both conventional ligands and a photoaffinity label. The chemical characteristics of the solubilized receptor will be determined. Interaction of the receptor with the membrane guanine nucleotide regulatory protein will be assessed. These studies will provide insight into the molecular mechanisms by which alpha-adrenergic receptors are coupled to adenylate cyclase. The results will provide further understanding of how catecholamines regulate platelet function and thus clarify the role of catecholamines in modulate platelet function in human disease.